Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Objective:To investigate the prevalence of sexual drug use in men who have sex with men (MSM) in Chengdu and analyze the relationship between depression and sexual drug use.Methods:A total of 1 277 MSM were recruited between November 2021 and May 2022. Questionnaire was used to collect information about their demographic characteristics, depression status and sexual drug use behavior. Univariate and multivariate logistic regression models were used to analyze the relationship between depression and sexual drug use.Results:In the 1 277 MSM, assessment identified 503 mild depression cases (39.4%), 196 moderate depression cases (15.3%) and 171 severe depression cases (13.4%) and 444 MSM (34.8%) reported sexual drug use in the past 6 months. Multivariate logistic regression models showed that compared with non-depression, mild depression (a OR=1.67,95% CI:1.24-2.23), moderate depression (a OR=1.50,95% CI: 1.02-2.19) and severe depression (a OR=1.56,95% CI:1.04-2.32) were positively associated with sexual drug use. Conclusions:The prevalence of depression and sexual drug use were high in MSM in Chengdu. There was a positive correlation between depression and sexual drug use. It is necessary to pay close attention to depression and sexual drug use and conduct targeted intervention in MSM.

Objective:To explore the potential risk factors for cancer in patients with adenomatous polyps based on tumor markers and polyp lesion characteristics.Methods:A retrospective analysis was conducted to collect clinical data of 115 patients with adenomatous intestinal polyps who visited Nanjing Jiangbei Hospital from November 2022 to November 2024. They were divided into a cancerous group (17 cases) and a non cancerous group (98 cases) based on whether they were cancerous or not. Clinical data such as tissue type and polyp site and tumor marker levels such as carcinoembryonic antigen (CEA) and cancer antigen 72-4 (CA72-4) were collected at the first visit of all patients. The potential risk factors of adenomatous intestinal polyp canceration were investigated by Logistic regression analysis.Results:Univariate analysis revealed that the proportion of villous tubular adenomas, central depression of polyps, and lobulated polyps in the cancerous group were higher than those in the non cancerous group. Serum levels of CEA and CA72-4 were also higher in the cancerous group than in the non cancerous group : 13/17 vs.47.96% (47/98), 7/17 vs. 15.31% (15/98), 6/17 vs. 8.16% (8/98), (6.41 ± 1.81) μg/L vs. (4.23 ± 1.48) μg/L, (6.98 ± 1.83) kU/L vs. (5.66 ± 1.78) kU/L, respectively. The difference was statistically significant ( P<0.05). The results of Logistic regression analysis showed that the histological subtype of villous tubular adenoma, central depression of polyps, lobulated polyps, and high levels of CEA and CA72-4 were independent risk factors for cancer in patients with adenomatous intestinal polyps ( P<0.05). A nomogram risk model was constructed based on the influencing factors of canceration in patients with adenomatous intestinal polyps. The calibration curve was drawn, and the calibration curve was similar to the Y-X straight line, suggesting that the evaluation results of the nomogram risk model were highly consistent with the actual observation results. The receiver operating characteristic (ROC) curve was drawn. The results showed that the area under the curve (AUC) of the nomogram risk model for evaluating the canceration of patients with adenomatous intestinal polyps was 0.956, and the evaluation value was high. The decision curve was drawn, with the threshold of high risk as the horizontal coordinate and the net rate of return as the vertical coordinate. The results showed that when the threshold was in the range of 0 - 0.85, 0.96 - 0.99, the net benefit rate of predicting the cancer risk of patients with adenomatous intestinal polyps was greater than 0 and the maximum net benefit rate was 0.148. Conclusions:The histological classification of villous tubular adenoma, central depression of polyps, lobulated polyps, and high levels of CEA and CA72-4 are independent risk factors for cancer in patients with adenomatous intestinal polyps; The evaluation efficiency of the column chart risk model constructed based on the above factors is good.

Objective To study the effect and molecular mechanism of vitamin D(VitD)on Tfh cells of MRL/lpr lupus mice.Methods C57/B6 mice and MRL/lpr lupus mice were transfected with siRNA to construct VDR knockout mouse models.Splenic Tfh cells of C57/B6 mice and MRL/lpr lupus mice were divided into control group,lupus group and VDRsiRNA lupus group(treated with vitamin D 0,1 and 10 nmol·L-1,respectively)by siRNA transfection.The percentage of Tfh cells was detected by flow cytometry.MRL/lpr lupus mice Peyer node Tfh cells were randomly divided into 7 groups,blank control group,vitamin D dose groups of 1 and 10 nmol·L-1,paricalcitol group(VitD 10 nmol·L-1+PA),VDRsiRNA control group,VDRsiRNA group(VitD 10 nmol·L-1),CaN inhibitor group(VitD 10 nmol·L-1+CsA),and incubated for 72 h.The concentration of calcium ions in Tfh of each group was detected.The expressions of AT1R,NFAT,CaN and P-CaN in Tfh cells were determined by Western blotting.Results The percentage of Tfh cells decreased significantly with the increase of vitamin D dose.Vitamin D CaN reduce the intracellular calcium concentration of Tfh,up-regulate the expression of AT1 protein in Tfh cells,and down-regulate the expression of CAN,P-CaN and NFAT protein in a dose-dependent manner,and the effect is more obvious when combined with PA.Conclusion Vitamin D may regulate the activation of follicular T helper cells in MRL/lpr mice via the Ca-CaN-NFAT pathway.

Objective:To investigate the prevalence of sexual drug use in men who have sex with men (MSM) in Chengdu and analyze the relationship between depression and sexual drug use.Methods:A total of 1 277 MSM were recruited between November 2021 and May 2022. Questionnaire was used to collect information about their demographic characteristics, depression status and sexual drug use behavior. Univariate and multivariate logistic regression models were used to analyze the relationship between depression and sexual drug use.Results:In the 1 277 MSM, assessment identified 503 mild depression cases (39.4%), 196 moderate depression cases (15.3%) and 171 severe depression cases (13.4%) and 444 MSM (34.8%) reported sexual drug use in the past 6 months. Multivariate logistic regression models showed that compared with non-depression, mild depression (a OR=1.67,95% CI:1.24-2.23), moderate depression (a OR=1.50,95% CI: 1.02-2.19) and severe depression (a OR=1.56,95% CI:1.04-2.32) were positively associated with sexual drug use. Conclusions:The prevalence of depression and sexual drug use were high in MSM in Chengdu. There was a positive correlation between depression and sexual drug use. It is necessary to pay close attention to depression and sexual drug use and conduct targeted intervention in MSM.

Objective:To construct a health education checklist for safety management of oral antitumor drugs in tumor patients, so as to provide a guidance for clinical nurses in practice, thereby improving the drug safety of patients taking oral antitumor drugs.Methods:Based on the cognition-behavior theoretical framework, a preliminary draft of a health education checklist for safety management of oral antitumor drugs in tumor patients was developed through literature review. The Delphi method was used to conduct consultations with 17 experts from July to September 2024 to revise and add or delete the contents of the checklist based on the experts' assignments of importance to the indicators at each level and the textual comments made.Results:A total of two rounds of expert consultation were conducted. The final established health education checklist for safety management of oral antitumor drugs in tumor patients included 4 primary and 28 secondary indicators. In the two rounds of consultation, the positive coefficient of experts was 100.0%, the coefficient of expert authority was 0.93, the coefficients of variation for the two rounds of expert ratings were 0 to 0.173 and 0 to 0.151, and the coefficients of Kendall's concordance were 0.141 (χ 2=74.461, P<0.001) and 0.113 (χ 2=59.549, P=0.002) , respectively. Conclusions:The health education checklist for safety management of oral antitumor drugs in tumor patients has good scientific, reliable and clinical practical value, which can provide scientific, standardized and convenient practical guidance for clinical nurses to implement health education on drug safety management for patients taking oral antitumor drugs.

Objective:To explore the potential risk factors for cancer in patients with adenomatous polyps based on tumor markers and polyp lesion characteristics.Methods:A retrospective analysis was conducted to collect clinical data of 115 patients with adenomatous intestinal polyps who visited Nanjing Jiangbei Hospital from November 2022 to November 2024. They were divided into a cancerous group (17 cases) and a non cancerous group (98 cases) based on whether they were cancerous or not. Clinical data such as tissue type and polyp site and tumor marker levels such as carcinoembryonic antigen (CEA) and cancer antigen 72-4 (CA72-4) were collected at the first visit of all patients. The potential risk factors of adenomatous intestinal polyp canceration were investigated by Logistic regression analysis.Results:Univariate analysis revealed that the proportion of villous tubular adenomas, central depression of polyps, and lobulated polyps in the cancerous group were higher than those in the non cancerous group. Serum levels of CEA and CA72-4 were also higher in the cancerous group than in the non cancerous group : 13/17 vs.47.96% (47/98), 7/17 vs. 15.31% (15/98), 6/17 vs. 8.16% (8/98), (6.41 ± 1.81) μg/L vs. (4.23 ± 1.48) μg/L, (6.98 ± 1.83) kU/L vs. (5.66 ± 1.78) kU/L, respectively. The difference was statistically significant ( P<0.05). The results of Logistic regression analysis showed that the histological subtype of villous tubular adenoma, central depression of polyps, lobulated polyps, and high levels of CEA and CA72-4 were independent risk factors for cancer in patients with adenomatous intestinal polyps ( P<0.05). A nomogram risk model was constructed based on the influencing factors of canceration in patients with adenomatous intestinal polyps. The calibration curve was drawn, and the calibration curve was similar to the Y-X straight line, suggesting that the evaluation results of the nomogram risk model were highly consistent with the actual observation results. The receiver operating characteristic (ROC) curve was drawn. The results showed that the area under the curve (AUC) of the nomogram risk model for evaluating the canceration of patients with adenomatous intestinal polyps was 0.956, and the evaluation value was high. The decision curve was drawn, with the threshold of high risk as the horizontal coordinate and the net rate of return as the vertical coordinate. The results showed that when the threshold was in the range of 0 - 0.85, 0.96 - 0.99, the net benefit rate of predicting the cancer risk of patients with adenomatous intestinal polyps was greater than 0 and the maximum net benefit rate was 0.148. Conclusions:The histological classification of villous tubular adenoma, central depression of polyps, lobulated polyps, and high levels of CEA and CA72-4 are independent risk factors for cancer in patients with adenomatous intestinal polyps; The evaluation efficiency of the column chart risk model constructed based on the above factors is good.

Objective To study the effect and molecular mechanism of vitamin D(VitD)on Tfh cells of MRL/lpr lupus mice.Methods C57/B6 mice and MRL/lpr lupus mice were transfected with siRNA to construct VDR knockout mouse models.Splenic Tfh cells of C57/B6 mice and MRL/lpr lupus mice were divided into control group,lupus group and VDRsiRNA lupus group(treated with vitamin D 0,1 and 10 nmol·L-1,respectively)by siRNA transfection.The percentage of Tfh cells was detected by flow cytometry.MRL/lpr lupus mice Peyer node Tfh cells were randomly divided into 7 groups,blank control group,vitamin D dose groups of 1 and 10 nmol·L-1,paricalcitol group(VitD 10 nmol·L-1+PA),VDRsiRNA control group,VDRsiRNA group(VitD 10 nmol·L-1),CaN inhibitor group(VitD 10 nmol·L-1+CsA),and incubated for 72 h.The concentration of calcium ions in Tfh of each group was detected.The expressions of AT1R,NFAT,CaN and P-CaN in Tfh cells were determined by Western blotting.Results The percentage of Tfh cells decreased significantly with the increase of vitamin D dose.Vitamin D CaN reduce the intracellular calcium concentration of Tfh,up-regulate the expression of AT1 protein in Tfh cells,and down-regulate the expression of CAN,P-CaN and NFAT protein in a dose-dependent manner,and the effect is more obvious when combined with PA.Conclusion Vitamin D may regulate the activation of follicular T helper cells in MRL/lpr mice via the Ca-CaN-NFAT pathway.

Objective:To construct a health education checklist for safety management of oral antitumor drugs in tumor patients, so as to provide a guidance for clinical nurses in practice, thereby improving the drug safety of patients taking oral antitumor drugs.Methods:Based on the cognition-behavior theoretical framework, a preliminary draft of a health education checklist for safety management of oral antitumor drugs in tumor patients was developed through literature review. The Delphi method was used to conduct consultations with 17 experts from July to September 2024 to revise and add or delete the contents of the checklist based on the experts' assignments of importance to the indicators at each level and the textual comments made.Results:A total of two rounds of expert consultation were conducted. The final established health education checklist for safety management of oral antitumor drugs in tumor patients included 4 primary and 28 secondary indicators. In the two rounds of consultation, the positive coefficient of experts was 100.0%, the coefficient of expert authority was 0.93, the coefficients of variation for the two rounds of expert ratings were 0 to 0.173 and 0 to 0.151, and the coefficients of Kendall's concordance were 0.141 (χ 2=74.461, P<0.001) and 0.113 (χ 2=59.549, P=0.002) , respectively. Conclusions:The health education checklist for safety management of oral antitumor drugs in tumor patients has good scientific, reliable and clinical practical value, which can provide scientific, standardized and convenient practical guidance for clinical nurses to implement health education on drug safety management for patients taking oral antitumor drugs.

Objective:To systematically retrieve, evaluate, and summarize evidence on insomnia screening and assessment in adult malignant tumor patients.Methods:The clinical decisions, guidelines, and expert consensus on screening and assessing insomnia in malignant tumor patients were systematically searched in clinical decision support systems, guideline websites, literature databases, and professional association websites. This study conducted methodological quality evaluation and evidence extraction, translation, and integration.Results:A total of 8 articles were included, including three clinical decisions, two evidence-based guidelines, and three expert consensuses. After extracting and summarizing evidence, 38 pieces of evidence were obtained from three aspects of general management principles, insomnia screening, and insomnia assessment.Conclusions:The insomnia screening and assessment in adult malignant tumor patients should be standardized according to evidence-based standards and combined with specific clinical situations in China.